This invention relates to a macular indentor for use in the treatment of subretinal neovascular membranes, and in particular to a macular indentor which is used to reduce vascular congestion in the treatment of subretinal neovascular membranes.
Age-related macular degeneration (AMD) is the leading cause of visual loss among adults aged 65 years or older in Western countries. Although neovascular AMD accounts for only 10% of all cases, it is responsible for 80% to 90% of legal blindness due to this disease and is the most common cause of choroidal neovascularization (CNV) in this age population. The pathological changes leading to CNV involve the complex of tissues in the choriocapilaris, Bruch's membrane, and the retinal pigment epithelium (RPE) with secondary involvement of the neurosensory retina. Essentially anything that alters the retinal pigment epithelium and Bruch's membrane can cause CNV. A variety of conditions other than AMD have been associated with CNV, including ocular histoplasmosis syndrome (POHS), pathologic myopia, angioid streaks, and idiopathic causes. Most histopathological studies have been performed in eyes with AMD. The histopathological feature common to many eyes that develop CNV is a break in Bruch's membrane. The capillary-like neovascularization originates from choroidal vessels and extends through these breaks. Age-related macular degeneration accounts for the largest group of patients with CNV. Most symptomatic CNV's are subfoveal and demonstrate an extremely poor natural history. Subfoveal neovascularization is defined as lesions lying under the geometric center of the foveal avascular zone (FAZ). Of untreated eyes followed for 2 years in a Macular Photocoagulation Study (MPS), only 5% had a final visual acuity better than 20/100, whereas 88% had a final visual acuity of 20/200 or worse. Laser photocoagulation has been the mainstay of therapy for choroidal neovascularization. Through a series of well-executed randomized, prospective clinical trials, the MPS established the superiority of photocoagulation over observation for CNV in a variety of settings. Specifically, photocoagulation treatment of extrafoveal and juxtafoveal neovascular membranes in AMD and other disorders was found to be beneficial compared to the no treatment group. In order to treat the entire area of CNV, the ophthalmologist has to be able to identify the boundaries of the choroidal neovascular membrane. Therefore, treatment is indicated only when the boundaries of the CNV are well demarcated. Unfortunately, occult or ill-defined new vessels are the most common pattern at presentation for exudative macular lesions in AMD. In one study, visible or classic neovascular membranes involved only 23% of eyes referred for treatment. The MPS, recently reported results of photocoagulation for subfoveal neovascular lesions in AMD showed benefit of laser treatment, but the difference between the treatment and observation groups was small and was seen only after two and five years. Also, as the laser energy destroys both the retina and subretinal membrane, there was a precipitous drop in visual acuity associated with treatment. These results underline both the poor natural history of the condition and the limitations of photocoagulation as a treatment modality.
Since the majority of CNV lesions associated with AMD are considered ineligible for laser treatment because of obscured boundaries, size and location, other options have been considered for treatment. One of these options is subretinal neovascular membrane removal using vitrectomy techniques. According to a study by Thomas and colleagues, neovascular membranes in AMD can indeed be removed, but the intrinsic growth patterns of the neovascular complexes limit the visual outcome in most eyes and does not appear to offer significant benefit over observation or laser photocoagulation. In this particular study, of 41 operated eyes, only 5% retained good central visual acuity of 20/40 or better, whereas visual acuity in 88% of the operated eyes were 20/200 or worse. Although the results after removal of choroidal neovascular membranes (CNM) associated with idiopathic and postinflamatory lesions are good, those associated with membranes secondary to angiod streaks and high myopia are similar to those seen in AMD. Clinical evidence and laboratory studies suggest that the integrity of the subfoveal retinal pigment epithelium (RPE) and choriocapillaris is one important factor in determining visual prognosis after submacular surgery. Gass has classified subfoveal membranes in patients with POHS by whether the CNM lies under the RPE (type 1) or between the RPE and the neurosensory retina (type 2). In AMD, the choroidal neovascular membrane is intimately associated with the RPE and the pigment epithelial cells are thus removed at the time of surgery in most patients. Laboratory studies demonstrate that persistent areas of bare, subfoveal RPE will lead to secondary atrophy of the choriocapillaris and outer retina. It is unlikely that refinement of surgical instrumentation will lead to further improvement in visual results in these eyes. Subretinal surgery might help in decreasing the size of the central scotoma at 6 months and 1 year, with remaining vision associated with the development of an eccentric fixation locus.
Interferon alpha-2a has been found to have an anti-angiogenesis effect in vitro and in vivo and is used clinically for the treatment of congenital hemangioma lesions. It has been used in the treatment of CNV from exudative AMD with sistemically administered doses of 3.0 to 6.0 million u/m of body surface area every other night for 8 to 12 weeks. The results have been so far disappointing with zero regression of the CNM in fluorescein angiography and a visual acuity less or equal to 20/200 in 10 patients in one series and no improvement of visual acuity with severe sistemic effects in 90% of 20 patients in another series.
Another technique in the treatment of subfoveal CNM which has been proposed by Coscas is the perifoveal and macular scatter photocoagulation. The first treatment modality was considered effective in preservation of visual acuity, but only if baseline acuity was 20/100 or worse, and also for a limited time. In the case of macular scatter photocoagulation, there was no statistical difference in visual acuity between treated and observed eyes.
Other approaches to the treatment of subfoveal choroidal neovascular membranes at an experimental level include vascular targeting with photodynamic occlusion of subretinal vessels, external beam radiotherapy on the macular region, and subretinal endophotocoagulation of choroidal neovascular membranes. Although some of these treatments appear to be promising, they still need further evaluation, testing, and refinement.
The relationship between AMD or chronic systemic hypertension, and disturbances of the choriocapillary bed in AMD has long been a subject of dispute. Histopathological studies have demonstrated consistent changes in the choroidal vascular bed in patients with AMD and it appears that alterations in the choroidal circulation with age are associated with the development of AMD. These changes include sclerosis of the choriocapillaris with thickening of the septa and narrowing of the lumen and replacement of the sinusoidal capillary network by a tubular system. Indeed, a significant association between AMD and systemic hypertension was demonstrated in human patients.
On the basis of the choroidal anatomy and pathophysiological abnormalities that involve the RPE, Bruch's membrane, and choriocapillaries in AMD, it is speculated that these elements become compromised by excessive permeability of the choroidal vessels. This hyperpermeability of the choroidal vessels leads to the formation of abnormal new vessels which pass through a break in Bruch's membrane to invade the subpigment epithelium and subsensory retinal space. By applying external pressure using a posterior buckle from the scleral side, the buckle attempts to decrease choroidal congestion under the macula and reduces vascular leakage thus preventing abnormal vessel proliferation. This procedure will not reverse the degenerative process of the RPE or destroy the neovascular membrane directly, but it is an attempt to stop or reduce the vascular leakage or hemorrhage that will ultimately lead to destruction of the photoreceptors.
As described above, one of the major limiting factors in successful treatment of subretinal neovascular membranes is the inability to reduce or decrease blood flow through the subretinal neovascular membrane. Thus, a device or treatment method which will reduce vascular congestion or decrease blood flow through the subretinal neovascular member would be advantageous. The present invention is therefore based upon the need and great interest to develop methods and constructions which obviate the limitations of currently available modes of therapies. An ideal device would be one in which bleeding could be reduced or neurosensory fluid accumulation could be reduced in the subretinal neovascular membrane. A device which can selectively indent the macular area of the eye to place pressure in the macular area is also an example of an ideal device. Additionally, combining a mechanical decongestion device with a local active agent that can stop vascular proliferation provides the best of both worlds.